| First Author | Hao F | Year | 2018 |
| Journal | J Immunol | Volume | 200 |
| Issue | 12 | Pages | 3905-3912 |
| PubMed ID | 29728506 | Mgi Jnum | J:263314 |
| Mgi Id | MGI:6164096 | Doi | 10.4049/jimmunol.1800115 |
| Citation | Hao F, et al. (2018) Abrogation of Lupus Nephritis in Somatic Hypermutation-Deficient MRL/lpr Mice. J Immunol 200(12):3905-3912 |
| abstractText | Systemic lupus erythematosus (SLE) is an autoimmune disease posing threats to multiple organs in the human body. As a typical manifestation of SLE, lupus nephritis is characterized by a series of pathological changes in glomerulus as well as accumulation of pathogenic autoreactive IgG with complement in the kidney that dramatically disrupts renal functions. Activation-induced deaminase (AID), which governs both somatic hypermutation (SHM) and class-switch recombination (CSR), has been shown to be essential for the regulation of SLE. However, the relative contributions of SHM and CSR to SLE pathology have not been determined. Based on the available AID(G23S) mice, we successfully established an AID(G23S) MRL/lpr mouse model, in which SHM is specifically abolished, although CSR is largely unaffected. We found that the abrogation of SHM effectively alleviated SLE-associated histopathological alterations, such as expansion of the mesangial matrix and thickening of the basement membrane of Bowman's capsule as well as infiltration of inflammatory cells. Compared with SLE mice, AID(G23S) MRL/lpr mice exhibited decreased proteinuria, blood urea nitrogen, and creatinine, indicating that the loss of SHM contributed to the recovery of renal functions. As a consequence, the life span of those SHM-deficient MRL/lpr mice was extended. Together, we provide direct evidence pinpointing a vital role of SHM in the control of SLE development. |
